Ryneze Liquid

SJ PHARMACEUTICALS, LLC
Great Southern Laboratories

Ryneze Liquid

FULL PRESCRIBING INFORMATION: CONTENTS*

• RYNEZE LIQUID DESCRIPTION:
• CLINICAL PHARMACOLOGY:
• RYNEZE LIQUID INDICATIONS AND USAGE:
• RYNEZE LIQUID CONTRAINDICATIONS:
• WARNINGS:
• PRECAUTIONS:
• Information for patients:
• Laboratory Tests:
• Drug Interactions:
• Carcinogenesis, Mutagenesis, Impairment of Fertility
• Pregnancy:
• Nursing Mothers:
• Pediatric Use:
• Geriatric Use:
• RYNEZE LIQUID ADVERSE REACTIONS:
• OVERDOSAGE:
• RYNEZE LIQUID DOSAGE AND ADMINISTRATION:
• HOW SUPPLIED:
• PRODUCT PACKAGING:

FULL PRESCRIBING INFORMATION

DESCRIPTION:

Each teaspoonful (5 mL) for oral administration contains:
Chlorpheniramine Maleate ...................................... 4 mg
Scopolamine Methyl Nitrate .............................. 1.25 mg

INACTIVE INGREDIENTS: Citric Acid, Grape flavor, Glycerin, Propylene Glycol, Purified Water, Sodium Citrate, Sodium
Saccharin, and Sorbitol.

RYNEZE® LIQUID contains ingredients from the following classes: antihistamine, and anticholinergic.

Chlorpheniramine Maleate is an antihistamine with the chemical name: 2-Pyridinepropanamine, γ-(4-chlorphenyl)-
N,N-dimethyl-, (Z)-2-butenedioate (1:1), and has the following chemical structure:

Scopolamine Methyl Nitrate is an anticholinergic belldonna alkaloid derivative with the chemical name:
[7(s)-(α ,2β,4β,5α,7β,)]–7–(3–hydroxy–1-oxo – 2- Phenylpropoxy)-9, 9-dimethyl–3-oxa– 9-azoniatricyclo
[3.3.1.0 2,4] nonane nitrate.It has the following chemical structure:

CLINICAL PHARMACOLOGY:

Chlorpheniramine maleate competitively antagonizes most of the smooth muscle stimulating actions of histamine on the
H1 receptors of the GI tract, uterus, large blood vessels, and bronchial muscle. It also antagonizes the action of histamine
that results in increased capillary permeability and the formation of edema. Chlorpheniramine maleate is analkylamine-type antihistamine.
This group of antihistamines are among the most active histamine antagonists and are
generally effective in relatively low doses. They thereby prevent, but do not reverse, responses mediated by histamine
alone. The anticholinergic actions of most antihistamines provide a drying effect on the nasal mucosa. These drugs are
not so prone to produce drowsiness and are among the most suitable agents for daytime use, but a significant proportion
of patients do experience this effect.

Scopolamine methyl nitrate is one of the principal anticholinergic/antispasmodic components of belladonna
alkaloids that exhibits antisecretory activity. Scopolamine methyl nitrate inhibits the muscarinic actions of acetylcholine
on structures innervated by postganglionic cholinergic nerves: smooth muscle, cardiac muscle, sinoatrial and
atrioventricular nodes, and exocrine glands. In general, the smaller doses of anticholinergics inhibit salivary and
bronchial secretions, sweating, and accommodation; cause dilation of the pupil; and may affect the heart rate.

INDICATIONS AND USAGE:

This product is indicated for the temporary relief of symptoms associated with seasonal and
perennial allergic and non-allergic rhinitis, and sinusitis.Chlorpheniramine Maleate temporarily relieves runny nose
and reduces sneezing, itching of the nose or throat, and itchy,watery eyes due to hay fever or other upper respiratory
allergies. Scopolamine Methyl Nitrate further augments the anti-secretory activity of this product.

CONTRAINDICATIONS:

This product is contraindicated in patients with hypersensitivity or idiosyncrasy to any of its
ingredients. It is also contraindicated in women who are pregnant or nursing.

It is also contraindicated in newborn or premature infants, because this age group has an increased susceptibility to the
anticholinergic side effects of chlorpheniramine maleate. Geriatric patients may be more sensitive to the effects of this medication.

Risk-benefit should be considered when the following conditions exist: Acute asthma; Bladder neck obstruction;
Brain damage in children; Cardiac disease, especially cardiac arrhythmias, congestive heart failure, coronary artery disease,
and mitral stenosis; Cardiovascular disease; Diabetes mellitus; Down’s Syndrome; Esophagitis, reflux; Narrow angle
glaucoma; Acute hemorrhage with unstable cardiovascular status; Hepatic function impairment; Hernia; Hypertension;
Hyperthyroidism; Intestinal atony in the elderly or debilitated patient; Chronic lung disease; Myasthenia gravis; Autonomic
neuropathy; Paralytic ileus; Prostatic hypertrophy; Psychiatric disorders; Pyloric obstruction; Renal function impairment;
Spastic paralysis, in children; Tachycardia; Toxemia of pregnancy; Ulcerative colitis; Urinary retention, or
predisposition to; Uropathy; Xerostomia.

WARNINGS:

This product may cause drowsiness or blurred vision. Patients taking this product should be warned not to
engage in activities requiring mental alertness such as operating a motor vehicle or other machinery or to perform
hazardous tasks while taking this drug.

Do not exceed recommended dosage.

Heat prostration can occur with the use of scopolamine methyl nitrate when the environmental temperature is high.
Diarrhea may be an early symptom of incomplete intestinal obstruction, especially in patients with ileostomy or
colostomy; in this instance, use of scopolamine methyl nitrate would be inappropriate and possibly harmful.

PRECAUTIONS:

General: Antihistamines have an atropine-like action and should be used with caution in
patients with a history of bronchial asthma, emphysema, increased intraocular pressure, hyperthyroidism,
cardiovascular disease and hypertension.

Use scopolamine methyl nitrate with caution in patients with hiatal hernia associated with reflux Esophagitis. Use
extreme caution and only when needed in patients with autonomic neuropathy, hyperthyroidism, coronary heart
disease, congestive heart failure, and cardiac arrhythmia.

Information for patients:

Patient consultation should include the following information regarding proper use of this medication:
• Do not take more medication than the amount recommended.
• This medication should be used with caution during exercise or hot weather, overheating may result in heat
stroke.
• Do not drive or operate machinery if drowsiness or dizziness occurs.
• Do not ingest alcoholic beverages, monoamine oxidase (MAO) inhibitors, or CNS depression producing
medications (hypnotics, sedatives, tranquilizers) while taking this medication.
• This medication possibly increases sensitivity of eyes to light.
• Scopolamine methyl nitrate may cause blurred vision.
• If a dose is missed, the medication should be taken as soon as possible unless it is almost time for the next
dose. Do not double dose.

Caution patients about the signs of potential side effects,
especially:
• Anticholinergic effects – clumsiness or unsteadiness;severe drowsiness; severe dryness of mouth, nose, or
throat; flushing or redness of face; shortness of breath or trouble breathing.
• Blood dyscrasias-sore throat and fever; unusual bleeding or bruising; unusual tiredness or weakness.
• Fast or irregular heartbeat.
• Psychotic episodes.
• Tightness in chest.

Note: When anticholinergics are given to patients, especially children, where the environmental temperature
is high there is a risk of a rapid increase in body temperature because of suppression of sweat gland
activity. Infants, patients with Down’s syndrome, and children with spastic paralysis or brain damage may show
an increased response to anticholinergics, thus increasing the potential for side effects.

Geriatric or debilitated patients may respond to usual doses of anticholinergics with excitement, agitation,
drowsiness, or confusion.

Laboratory Tests:

The following may be especially important in patient monitoring (other tests may be
warranted in some patients, depending on conditions): Blood pressure determination – recommended at
frequent intervals during therapy: Electrocardiogram (ECG) – monitoring may be required: Intraocular
pressure determination – recommended at periodic intervals, as these medications may increase the
intraocular pressure.

Drug Interactions:

Do not take this product if you are presently taking, or have taken within the preceding
two weeks, a prescription drug for high blood pressure or depression without first consulting your physician.
Absorption of other oral medications may be decreased during concurrent use with anticholinergics
due to decreased gastrointestinal motility and delayed gastric emptying.

Combinations containing any of the following medications, depending on the amount present, may
also interact with this product:
• Alkalizers, such as: calcium and/or magnesium-containing antacids; Carbonic inhibitors;
citrates; sodium bicarbonate-urinary excretion of anticholinergics may be delayed by alkalization of the
urine, thus potentiating scopolamine methyl nitrate therapeutic and/or side effects.
• Antacids or adsorbent antidiarrheals-simultaneous use of these medications may reduce absorption of
scopolamine methyl nitrate, resulting in decreased therapeutic effectiveness; doses of these should be
spaced 2 or 3 hours apart from doses of scopolamine methyl nitrate.
• Anticholinergics – Concurrent use with anticholinergic effects; patients should be advised to report
occurrence of gastrointestinal problems promptly since paralytic ileus may occur with concurrent therapy.
• CNS Depressants – Concurrent use of alcohol, antihistamines with alcohol, tricyclic antidepressants,
barbiturates and other CNS depressants may have an additive effect.
• Ketoconazole – Anticholinergics may increase gastrointestinal pH, possibly resulting in a marked
reduction in ketoconazole absorption during concurrent use with anticholinergics; patients should be advised
to take these medications at least 2 hours after ketoconazole.
• MAO inhibitors – Concurrent use may prolong and intensify cardiac stimulate and vasopressor effects of
chlorpheniramine, resulting in headache, cardiac arrhythmias, vomiting or sudden and severe
hypertensive and/or hyperpyretic crisis. These medications should not be administered during
or within 14 days following the administration of MAO inhibitor therapy.
• Metoclopramide – Concurrent use of metoclopramide with anticholinergics may antagonize
metoclopramide’s effects on gastrointestinal motility.
• Potassium chloride – Concurrent use with anticholinergics may increase the severity of
potassium chloride-induced gastrointestinal lesions.

Carcinogenesis, Mutagenesis, Impairment of Fertility

No data is available on the long-term potential of the components of this product for Carcinogenesis, Mutagenesis or Impairment of Fertility in animals or humans.

Pregnancy:

Category C: It is not known whether Ryneze® Liquid can cause fetal harm when administered
to a pregnant woman or can affect reproduction capacity. Ryneze® Liquid should be given to a pregnant
woman only if clearly needed.

Nursing Mothers:

It is not known whether this drug is excreted in human milk. Because many drugs are excreted
in human milk, caution should be exercised when Ryneze Liquid is administered to a nursing woman.

Pediatric Use:

Safety and effectiveness of Ryneze® Liquid in children below the age of 6 have not been established.

Use is not recommended for children under six years of age. A paradoxical reaction characterized by
hyperexcitability may occur in children taking large doses of anticholinergics.

Geriatric Use:

Geriatric patients may respond to usual doses of anticholinergics with excitement, agitation,
drowsiness, or confusion. Geriatric patients are especially susceptible to the anticholinergic side effects,
such as constipation, dryness of the mouth, and urinary retention (especially in males). If these side effects occur
and continue or are severe, medication should probably be discontinued.

Caution is also recommended when anticholinergics are given to geriatric patients, because of the danger of
precipitating undiagnosed glaucoma. Memory may become severely impaired in geriatric patients, with the
continued use of anticholinergics, since these drugs block the action of acetylcholine, which is responsible for
many functions of the brain, including memory function.

ADVERSE REACTIONS:

The following adverse reactions have been observed with the use of chlorpheniramine and
scopolamine methyl nitrate; Arrhytmias, blood dyscrasias, CNS depression, CNS stimulation, dizziness, drowsiness,
dryness of mouth, hallucinations, hypotension, hypertension, increased sweating, loss of appetite,
paradoxical reaction, restlessness, skin rash, stomach upset or pain, thickening of mucus, tingling in hands or
feet, trembling, troubled breathing, unusual tiredness or weakness, vomiting.

Note: Agitation; confusion; difficult or painful urination; drowsiness; dizziness; and dryness of mouth, nose and
throat are more likely to occur in the elderly. Nightmares, unusual excitement, nervousness,
restlessness, or irritability are more likely to occur in children and the elderly. When anticholinergics are given
to patients, especially children, where the environmental temperature is high, there is risk of a rapid increase in
body temperature.

OVERDOSAGE:

In all cases of suspected overdose, immediately call your regional poison center and/or
contact a physician immediately. The stomach should be emptied promptly by lavage or induction of emesis with
syrup of ipecac. The installation of activated charcoal into he stomach also should be considered. The treatment of
overdose is essentially sypmptomatic and supportive. If respiratory depression is present treat promptly with oxygen and/or
mechanical support of ventilation. If convulsions or marked CNS excitement occurs, only short-acting benzodiazepine-type
drugs should be used.

DOSAGE AND ADMINISTRATION:

Adults and children 12 years of age and older:

1 teaspoonful (5 mL) every 4 to 6 hours, not to exceed 6 teaspoonfuls in 24 hours.

Children 6 to under 12 years of age:

½ teaspoonful (2.5 mL) every 4 to 6 hours, not to exceed 3 teaspoonfuls in 24 hours.

RYNEZE® LIQUID is not recommended for children under 6 years of age.

Note:Geriatric patients may be more sensitive to the effects of the usual adult dose. Adjust adult dose accordingly.

HOW SUPPLIED:

RYNEZE® LIQUID is supplied as a clear, grape-flavored liquid, dye free, sugar free, alcohol
free, and gluten free in 16 fl oz (473 mL) bottles, NDC 24839-346-16, and 10 mL sample,
NDC 24839-346-10

Pharmacist: Store at controlled room temperature, 15°-30°C (59°-86°F). Avoid exposure to heat. Dispense
in a tight, light-resistant container as defined in the USP/NF with a child-resistant closure.

PRODUCT PACKAGING:

The packaging below represents the labeling currently used.

Ryneze ® Liquid

Antihistamine/Anticholinergic

Each 5 mL (one teaspoonful) for oral
administration contains:
Chlorpheniramine Maleate ...... 4 mg
Scopolamine Methyl Nitrate .... 1.25 mg

Rx Only

Dye Free/Sugar Free
Alcohol Free/Gluten Free
Grape Flavor
16 fl oz (473 mL)

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Ryneze Liquid Chlorpheniramine maleate, Scopolamine Methyl Nitrate LIQUID Product Information Product Type Human prescription drug label Item Code (Source) NDC:24839-346 Route of Administration ORAL DEA Schedule Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength Chlorpheniramine Maleate CHLORPHENIRAMINE 4 mg Methscopolamine Nitrate Methscopolamine 1.25 mg Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:24839-346-10 10 in 1 BOTTLE 2 NDC:24839-346-16 473 in 1 BOTTLE Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date 2009-07-09